• Cefazolin: Therapeutic Uses and Clinical Applications

  • Cefazolin is a drug of choice for prophylaxis in many/most clean and clean-contaminated surgical procedures.^2,3 

    • Rationale⁴

      • Cefazolin covers the most common skin flora (S. aureus, S. epidermidis) and enteric organisms (E. coli) likely to contaminate surgical sites.

        • The 1.8-hour half-life allows for protection throughout most short-to-medium duration surgeries with a single dose, and its narrow spectrum minimizes collateral damage to the patient's microbiome which, for example reduces C. difficile risk compared to broad-spectrum agents like ceftriaxone or carbapenems.

    • Surgical Procedures

      • Cardiothoracic: primary agent for coronary artery bypass graft (CABG), valve replacement, and insertion of pacemakers.

      • Orthopedic: principal agent for joint arthroplasty, fracture fixation as well as spinal surgery.

      • General Surgery: gastroduodenal, biliary and hernia repair.

      • OB/GYN: C-sections and hysterectomies.

      • Head and Neck Surgeries: Clean-contaminated procedures. (A "clean-contaminated" wound describes the surgery when respiratory, digestive or genitourinary tracks are entered under controlled conditions. This approach is associated with the higher infection risk compared to clean wounds.)

    • Infective Endocarditis

      • Haemophilus parainfluenzae Endocarditis

        Description: Gross pathology of subacute bacterial endocarditis involving mitral valve. Left ventricle of heart has been opened to show mitral valve fibrin vegetations due to infection with Haemophilus parainfluenzae. Autopsy. Content Providers(s): CDC/Dr. Edwin P. Ewing, Jr. Creation Date: 1972 Attribution Public Domain https://phil.cdc.gov/PHIL_Images/02122002/00007/PHIL_851_lores.jpg

      • For Methicillin-Sensitive Staphylococcus aureus bacteria (MSSA endocarditis, cefazolin has evolved from an "alternative" to a "preferred" agent for many clinicians, particularly for patients with penicillin allergies or those who cannot tolerate the adverse effects of anti-staphylococcal penicillins (ASPs).

      • Native Valve Endocarditis (MSSA)

        • Regimen: Vefazolin IV every 8 hours for 6 weeks

        • Rationale:  Studies and meta-analyses suggest cefazolin has similar cure rates to nafcillin for MSSA bacteremia and endocarditis, with significantly lower rates of nephrotoxicity.^5,6 

        • Special consideration

          •  For severe, life-threatening endocarditis with large vegetations, some  experienced clinicians still prefer nafcillin due to possible risk of the inoculum effect with cefazolin.^7,8 

      • Prosthetic Valve Endocarditis⁹  

        • Used in combination with Rifampin (for biofilm penetration) and Gentamicin (for initial synergy), typically for 6 weeks.

          • This protocol mimics the nafcillin protocol of  Cefazolin + Rifampin + Gentamicin.

    • Skin and Soft Tissue Infections (SSTIs)

      • Dosing¹⁰

        • Cefazolin is highly effective for cellulitis¹¹, erysipelas¹², and abscesses caused by MSSA and Group A Streptococcus.¹²

    • Osteomyelitis and Septic Arthritis

      • Cephalothin exhibits both good bone penetration and reliable activity against S. aureus.

        •  Accordingly, cefazolin is effective for treating osteomyelitis.¹³

          • Culture and sensitivity testing from the infective site in form the selection of the most appropriate antimicrobial for management of osteomyelitis.^14,15

    • Urinary Tract Infections (UTIs)

      • Cefazolin effectively treats uncomplicated UTIs (cystitis, pyelonephritis) caused by susceptible E. coli, P. mirabilis, and Klebsiella.¹⁶

        • Surrogate Testing

          • Clinical microbiology laboratories often use cefazolin susceptibility as a surrogate marker to predict susceptibility to oral cephalosporins (like cephalexin) for uncomplicated UTIs.¹⁶

        • Pregnancy

          • Cefazolin appears to be a safe option for treating pyelonephritis in pregnant women, avoiding the risks of fluoroquinolones or aminoglycosides.¹⁷

            • Cefazolin is categorized (AU TGA pregnancy category B1): "Drugs which have been taken by only limited number of pregnant women in women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have not shown evidence of an increased occurrence of fetal damage."¹⁸

            •   Cefazolin is categorized (US FDA pregnancy category: B) "Animal reproduction studies have failed to demonstrate risk to the fetus and there are no adequate and well-controlled studies in pregnant women."¹⁸

    • Bacteremia (Bloodstream Infections)

      • Cefazolin appears appropriate for use for uncomplicated and complicated MSSA bacteremia.¹⁹

• Cefazolin: Adverse Reactions and Safety Profile²⁰

  • Similar to other beta-lactams, cefazolin is generally well-tolerated.

    • The most common adverse reactions are hypersensitivity reactions, which range from mild skin rashes and urticaria to severe anaphylaxis.

    • Other potential adverse effects include gastrointestinal disturbances such as nausea and diarrhea, transient elevations in liver enzymes, leukopenia, neutropenia, and, rarely, renal toxicity.

    • Prolonged use can, as with other broad-spectrum antibiotics, predispose to superinfections such as Clostridioides difficile–associated diarrhea.

December 2025